CFTR OPEN PROJECT

CFTR Open Project

Creating a high activity CFTR mutant

R104C CFTR

Cui et al (2014) made single channel recordings with oocytes expressing CFTR with two engineered cysteines (R104C/E116C) and observed that the channel was locked in the open state. When DTT was applied from the extracellular side, the R104C/E116C CFTR channel closed, suggesting that C104 and C116 spontaneously form a disulfide bond and lock the channel in the open state. Cui et al (2014) observed true channel closures in single channel recordings of R104C/E116C CFTR in the absence of DTT, and ATP and PKA were required for activation of R104C/E116C CFTR, suggesting the disulfide bond between 104 and 116 is broken when the NBDs separate and TMDs form the closed state. It can also be locked into the closed state with the M2M molecular linker.

CFTR exhibits similarities and differences with other anion channels.

Therefore, We can build open state models by ruining Modeller with certain distance constraints. Then we used the open stat models from Modeller to find promising residue pairs.

Subpages (1): Build CFTR open state using Modeller